Posterior cortical atrophy (PCA), also called Benson's syndrome, is a rare form of
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
which is considered a visual variant or an atypical variant of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(AD).
The disease causes
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
of the
posterior part of the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
, resulting in the progressive disruption of complex
visual processing
Visual processing is a term that is used to refer to the brain's ability to use and interpret visual information from the world around us. The process of converting light energy into a meaningful image is a complex process that is facilitated by ...
.
PCA was first described by D. Frank Benson in 1988.
PCA usually affects people at an earlier age than typical cases of Alzheimer's disease, with initial symptoms often experienced in people in their mid-fifties or early sixties.
This was the case with writer
Terry Pratchett
Sir Terence David John Pratchett (28 April 1948 – 12 March 2015) was an English humourist, satirist, and author of fantasy novels, especially comical works. He is best known for his ''Discworld'' series of 41 novels.
Pratchett's first nov ...
(1948–2015), who went public in 2007 about being diagnosed with PCA. In rare cases, PCA can be caused by
dementia with Lewy bodies
Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time ...
and
Creutzfeldt–Jakob disease
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, ...
.
Symptoms
The main symptom resulting from posterior cortical atrophy is a decrease in
visuospatial and visuoperceptual capabilities, since the area of atrophy involves the
occipital lobe
The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head".
The occipital lobe is the vi ...
responsible for
visual processing
Visual processing is a term that is used to refer to the brain's ability to use and interpret visual information from the world around us. The process of converting light energy into a meaningful image is a complex process that is facilitated by ...
.
The atrophy is progressive; early symptoms include difficulty reading, blurred vision, light sensitivity, issues with depth perception, and trouble navigating through space.
Additional symptoms include
apraxia
Apraxia is a motor disorder caused by damage to the brain (specifically the posterior parietal cortex or corpus callosum), which causes difficulty with motor planning to perform tasks or movements. The nature of the damage determines the disorder' ...
, a disorder of movement planning,
alexia, an impaired ability to read, and
visual agnosia Visual agnosia is an impairment in recognition of visually presented objects. It is not due to a deficit in vision (acuity, visual field, and scanning), language, memory, or intellect. While cortical blindness results from lesions to primary visual ...
, an object recognition disorder.
In the
two-streams hypothesis
The two-streams hypothesis is a model of the neural processing of vision as well as hearing. The hypothesis, given its initial characterisation in a paper by David Milner and Melvyn A. Goodale in 1992, argues that humans possess two distinct visu ...
, damage to the
ventral, or "what" stream, of the
visual system
The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight (the a ...
, located in the
temporal lobe
The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe ...
, leads to the symptoms related to general vision and object recognition deficits; damage to the
dorsal, or "where/how" stream, located in the
parietal lobe
The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus.
The parietal lobe integrates sensory informa ...
, leads to PCA symptoms related to impaired movements in response to visual stimuli, such as navigation and apraxia.
As
neurodegeneration
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
spreads, more severe symptoms emerge, including the inability to recognize familiar people and objects, trouble navigating familiar places, and sometimes visual hallucinations.
In addition, difficulty may be experienced in making guiding movements towards objects, and a decline in literacy skills including reading, writing, and spelling may develop.
Furthermore, if neural death spreads into other anterior cortical regions, symptoms similar to
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, such as memory loss, may result.
In PCA where there is significant
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
in one hemisphere of the brain
hemispatial neglect
Hemispatial neglect is a neuropsychological condition in which, after damage to one hemisphere of the brain (e.g. after a stroke), a deficit in attention and awareness towards the side of space opposite brain damage (contralesional space) is obser ...
may result – the inability to see stimuli on one half of the visual field.
Anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
and
depression are also common symptoms.
Connection to Alzheimer's disease
Studies have shown that PCA may be a variant of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(AD), with an emphasis on visual deficits.
Although in primarily different, but sometimes overlapping, brain regions, both involve progressive neural degeneration, as shown by the loss of neurons and synapses, and the presence of
neurofibrillary tangle
Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is kn ...
s and
senile plaques
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of micr ...
in affected brain regions; this eventually leads to
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
in both diseases.
In PCA there is more cortical damage and
gray matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distinguis ...
(cell body) loss in posterior regions, especially in the occipital, parietal, and temporal lobes, whereas in Alzheimer's there is typically more damage in the
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...
and
hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
.
PCA tends to impair
working memory
Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
and
anterograde memory, while leaving
episodic memory
Episodic memory is the memory of everyday events (such as times, location geography, associated emotions, and other contextual information) that can be explicitly stated or conjured. It is the collection of past personal experiences that occurred ...
intact, whereas in AD there is typically impaired episodic memory, suggesting some differences still lie in the primary areas of cortical damage.
Over time, however, atrophy in PCA may spread to regions that are commonly damaged in AD, leading to shared AD symptoms such as deficits in memory, language, learning, and cognition.
Although PCA has an earlier onset, a diagnosis with Alzheimer's is often made, suggesting that the degeneration has simply migrated anteriorly to other cortical brain regions.
There is no standard definition of PCA and no established diagnostic criteria, so it is not possible to know how many people have the condition. Some studies have found that about 5 percent of people diagnosed with Alzheimer's disease have PCA. However, because PCA often goes unrecognized, the true percentage may be as high as 15 percent. Researchers and physicians are working to establish a standard definition and diagnostic criteria for PCA.
PCA may also be correlated with
Lewy body disease
Lewy body dementias are two similar and common subtypes of dementia—dementia with Lewy bodies (DLB) and
Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The two conditions have sim ...
,
Creutzfeldt–Jakob disease
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, ...
,
Bálint's syndrome
Bálint's syndrome is an uncommon and incompletely understood triad of severe neuropsychological impairments: inability to perceive the visual field as a whole (simultanagnosia), difficulty in fixating the eyes (oculomotor apraxia), and inability ...
, and
Gerstmann syndrome
Gerstmann syndrome is a neuropsychological disorder that is characterized by a constellation of symptoms that suggests the presence of a lesion usually near the junction of the temporal and parietal lobes at or near the angular gyrus. Gerstman ...
.
In addition, PCA may result in part from mutations in the presenilin 1 gene (
PSEN1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the ''PSEN1'' gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta ( ...
).
Diagnosis
The cause of PCA is unknown, and there are no fully accepted diagnostic criteria for the disease.
This is partially due to the gradual onset of PCA symptoms, their variety, the rare nature of the disease, and the younger age of onset typically 50–60 years.
In 2012, the first international conference on PCA was held in Vancouver, Canada. Continued research and testing will hopefully result in accepted and standardized criteria for diagnosis.
PCA is often initially misdiagnosed as an
anxiety disorder
Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
or
depression. It has been suggested that depression or anxiety may result from the symptoms of decreased visual function, and the progressive nature of the disease. Early visual impairments have often led to a referral to an
ophthalmologist
Ophthalmology ( ) is a surgery, surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders.
An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Followin ...
, which can result in unnecessary cataract surgery.
Due to the lack of
biomarkers
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
for PCA, neuropsychological examinations are advised.
Neuroimaging
Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incre ...
can also assist in the diagnosis of PCA.
For PCA and AD neuroimaging is carried out using
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
scans,
single-photon emission computed tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
, and
positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
(PET scans).
Neuroimages are often compared to those of people with AD to assist diagnosis. Due to the early onset of PCA in comparison to AD, images taken at the early stages of the disease will vary from brain images in AD. At this early stage brain
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
will be shown to be more centrally located in the right
posterior lobe
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...
and occipital gyrus, while AD brain images show the majority of atrophy in the medial
temporal cortex
The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe is involved in proc ...
. This variation within the images will assist in early diagnosis of PCA; however, as the years go on the images will become increasingly similar, due to the majority of PCA also developing to AD later in life because of continued brain
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
.
A key aspect found through brain imaging of PCA patients is a loss of
grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...
(collections of neuronal cell bodies) in the posterior and occipital temporal cortices within the right hemisphere.
For some people with PCA, neuroimaging may not give a clear diagnosis; therefore, careful observation in relation to PCA symptoms can also assist in the diagnosis.
The variation and lack of organized clinical testing has led to continued difficulties and delays in the diagnosis of PCA.
Treatment
Specific and accepted treatment for PCA has yet to be discovered; this may be due to the rarity and variations of the disease.
At times people with PCA are treated with AD treatments, such as cholinesterase inhibitors,
donepezil
Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's disease, Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, ha ...
,
rivastigmine
Rivastigmine (sold under the trade name Exelon among others) is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces th ...
,
galantamine
Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid that has been isolated from the bulbs and flowers of ''Galanthus nivalis'' (Common snowdro ...
, and
memantine
Memantine is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.
Common side effects include headache, constipation, sleepiness, and dizziness. Severe side effects may include blood clots ...
.
Antidepressant drugs have also provided some positive effects.
Other treatments such as
occupational therapy
Occupational therapy (OT) is a global healthcare profession. It involves the use of assessment and intervention to develop, recover, or maintain the meaningful activities, or ''occupations'', of individuals, groups, or communities. The field of ...
, or help with adapting to visual changes may help.
People with PCA and their caregivers are likely to have different needs than the more typical cases of Alzheimer's disease, and may benefit from specialized support groups, or other groups for young people with dementia. No study to date has been definitive to provide accepted conclusive analysis on treatment options.
References
External links
Posterior Cortical Atrophy supportfrom the
Dementia Research Centre
The UCL Queen Square Institute of Neurology is an institute within the Faculty of Brain Sciences of University College London, University College London (UCL) and is located in London, United Kingdom. Together with the National Hospital for Neur ...
{{CNS diseases of the nervous system
Central nervous system disorders
Aging-associated diseases
Ailments of unknown cause
Unsolved problems in neuroscience
1988 in science